Customized Ablations #2: The Future is Close

This is the second of a series of eight articles chronicling the development of Customized Ablation or Wavefront Driven LASIK. This column contains my thoughts from the 1999 AAO meeting, and was published in the February 15, 2000 issue of Ocular Surgery News.

Customized Ablations: The Future is Close

Technology Update

Irving J. Arons
Managing Director
Spectrum Consulting

At last year's AAO meeting (1998), we learned of the first hints of customized ablations, as several firms announced plans to tie corneal topography to their lasers and use this diagnostic input to drive the ablation program. In addition, as I reported in the June 15th issue of OSN, Autonomous Technologies (Orlando, FL) was leading the way in going beyond topography to wavefront analysis, in other words, measuring all of the aberrations of the eye and using that data to not only achieve emmetropia, but to go beyond 20/20 vision and achieve "eagle-like" vision.

Well, technology has taken a major leap forward. Forget topography-driven ablations -- although it will make a difference in treating corneal defects like unequal/astigmatic corneas -- but wavefront/ray tracing analysis is closer than any of us thought. At this year's AAO meeting, I witnessed demonstrations on no less than three new wavefront and one new ray tracing devices. In addition, the Autonomous wavefront device, in conjunction with its LadarVision excimer, has now been used to treat human eyes, as Marguerite McDonald, MD, reported on the very early results of her first 5 patients, treated in September; while Theo Seiler, MD, of Dresden, Germany reported on his first dozen patients, treated in July and August, using his Dresden Wavefront Analyzer and the WaveLight (Erlangen, Germany) Allegretto scanning spot excimer laser. (The Dresden Wavefront Analyzer will also be used with a new small spot scanning laser about to be introduced by Schwind eye-tech-solutions GmbH of Kleinostheim, Germany.)

In addition to the Autonomous CustomCornea Measurement Device and the Dresden Wavefront Analyzer, to be developed and distributed by Technomed GmbH of Baesweiler, Germany, VISX (Santa Clara, CA) unveiled Josef Bille's 20/10 Perfect Vision (Heidelberg, Germany) wavefront device, and Bausch & Lomb Surgical (Claremont, CA) demonstrated a prototype of its aberrometer/wavefront analyzer (developed by Technolas GmbH of Munich, to be coupled with its Technolas 217C excimer laser, that appears to operate in a similar fashion to other wavefront devices. It is my understanding that the aberrometer will probable be incorporated into B&L's Orbtek (Salt Lake City, UT) Orbscan device, to provide maximum information about both the cornea and internal aberrations of the eye system. (Again, this was hinted at by Tim Turner of Orbtek, in his talk last Spring that I reported on in the June 15th issue of OSN.) I also saw a demonstration of a new ray trace device from Tracey Technologies (Bellaire, TX), formed by Joseph Wakil, formerly of EyeSys, to commercialize this new device developed at the Institute of Biomedical Engineering in Kiev, Russia. The device was discovered by Ioannis Pallikaris, MD, of Greece, who used it to run some of the first experiments on human eyes at the University Hospital of the University of Crete, and is a co-founder of Tracey Technologies. The Tracey device is an electro-optical interferometric analyzer that measures refraction in real time, to ±0.20 diopters, and according to its developers, may be more versatile in measuring aberrations of the eye than the wavefront devices.

So, instead of being overwhelmed by topolinked lasers, I was overwhelmed instead by the next generation of analyzers, wavefront and ray tracing. It appears that some of these devices will be available as soon as this Spring's ASCRS meeting, as a diagnostic tool to gather more complete refraction information, i.e., a better refraction, which can than be fed into current excimer laser's ablation programs for achieving a higher percentage of 20/20 corrections than can be done today. However, it will probably be several years before wavefront-linked customized ablations will be routinely available for general use. In the meantime, topographic links are still moving forward, with several laser companies not yet working with wavefront technologies, striving to establish relationships with topography companies or devices. (See the accompanying table for listing of which analytical/diagnostic devices each of the excimer laser companies is currently pursuing.)

The New Technologies

Summit Technology/Autonomous Technologies

Autonomous has spent over three years working on its CustomCornea wavefront measuring device. These efforts are starting to bear fruit, with the first patients treated using the system, and the FDA accepted the company's IDE for CustomCornea last July. The first of 40 patients have been enrolled in a Phase II-like feasibility study to determine calibration and safety, with doctors treating one eye with LASIK, and the other with CustomCornea-controlled LASIK. In Dr. McDonald cases, she was able to objectively measure the unique aberrations of each patient's eye and treat the CustomCornea eye with an individualized ablation pattern to correct for those aberrations. Autonomous expects that it will take 1 to 2 years to complete its Phase III clinicals and be ready to submit data to the FDA. However, the company expects to be able to market a stand-alone diagnostic device sometime next year, which laser users will be able to use to achieve better refractions to feed into the laser's ablation program.

Autonomous believes that it has an advantage over others working with wavefront technologies, because of its LadarVision system and its unique eye tracker. The company believes that the combination of a small spot scanning laser and the ability to place the correction precisely where it is needed gives it a step up on its competition.

VISX/20/10 Perfect Vision

At a presentation sponsored by VISX, Josef Bille, the founder of 20/10 Perfect Vision, explained how he got involved in developing his wavefront analyzer, which will be marketed by VISX under an exclusive worldwide agreement. Bille, the Director of the Institute of Applied Physics at the University of Heidelberg, and a founder of both Heidelberg Engineering and Intelligent Surgical Laser (ISL), originally developed the technology for use in astronomical applications in the mid 1970s, with the first German patents filed in 1982 and issued in 1986. In 1997 through 1999, he co-founded 20/10 Perfect Vision, and filed additional patents covering his later developments. The technology is based on adaptive optics to compensate for aberrations, using a deformable mirror, which has been reduced in size to a microchip array today, and speeds up the testing time to less than 15 seconds. A laser signal is imposed onto the retina and the return signal is analyzed using a CCD device to form an acuity map and a differential acuity map, which are used to achieve a simulation of best acuity. In this way, the device can analyze the refractive state of the eye, and the output can be used to make a more exact contour ablation of the cornea. VISX intends to incorporate the technology into a diagnostic device, which they hope to make commercially available in 2000.

The real question is how VISX intends to couple the diagnostic tool to their laser. According to experts in the field, a rapid firing, small spot scanning laser is needed to place a precise ablation pattern on the cornea, and a rapid-response tracking device is needed for this precise placement. VISX currently can scan a small spot, but at a rather slow scanning rate (50 Hz), and does not, to my knowledge, have a precise tracking device for their laser system. Perhaps, they will acquire the needed technologies in order to commercialize their wavefront technology for performing customized ablations.

According to a VISX spokesperson, the company plans to deliver active eye tracking and rapid small spot scanning capabilities in fiscal year 2000. The STAR S2 has already demonstrated its ability to deliver ablations as small as 1 mm in diameter via its CAP Method for the treatment of irregular corneas (currently available for international use only). Theoretically, it would not even be necessary to complete an entire custom ablation with a small spot, but rather through a combination of broad area (not beam) ablations followed by small-spot "contouring" method.

The Dresden Wavefront Analyzer/TechnoMed Technology

Developed by Theo Seiler and his colleagues at the Department of Ophthalmology, University Eye Clinic, Dresden, Germany, the Dresden Wavefront Analyzer is based on the Tschernig aberroscope, first described in 1894. A bundle of equidistant light rays are projected onto the cornea, and due to optical imaging, become focused on the retina. In an aberration-free eye, the retinal image pattern consists of equidistant light spots. However, the spot pattern of a normal eye is distorted, according to the ocular aberrations. The deviation of all spots from the ideal pattern is measured by an indirect ophthalmoscope and directed to low-light CCD linked to a computer, and these patterns are used to compute wavefront aberrations in the form of Zernike polynomials. When compared with and integrated with pre-operative corneal topography, an ablation profile is computed and used to feed the excimer laser to correct for all of the eye's aberrations. By reducing the ocular aberrations, and adjusting for the differential effects of the pupil size, the visual acuity can be dramatically improved, approaching 20/15 vision or better.

The Dresden Wavefront Analyzer uses a frequency-doubled Nd:YAG laser at 532 nm and a mask system to create 168 equidistant and parallel light rays for projection onto the cornea. The overall exposure time is 40 ms. The precision of the device allows for an objective measurement of spherical and cylindrical refractive error with an accuracy of better than ±0.25 diopters.

The device will be marketed by TechnoMed Technology and will be coupled with excimer laser systems from both WaveLight Laser Technologies AG and Schwind eye-tech-solutions GmbH.

WaveLight Laser Technologies AG

The Dresden Wavefront Analyzer has been used with WaveLight's Allegretto excimer laser to treat the first human patients, beginning in March 1999. In July, Professor Dr. Theo Seiler used the system to treat the first patients under the WaveLight protocol. The post-operative vision of the first seven patients was 2-3 times as sharp as that of a normally-sighted (20/20)person. Of the first 12 patients treated, 3 have achieved 20/15; 2 are at 20/10; and 1 had achieved 20/8. Anecdotaly, Dr. Seiler told of the woman that he had treated who reached 20/8 acuity. The doctors in attendance were overwhelmed by her visual acuity but, the woman complained that she was unhappy with her new vision, as she could no longer watch television. It seemed that instead of seeing the clear pictures on the screen, she was now seeing the raster lines! Since then, additional patients have achieved 20/8 acuity without that particular problem.

It is expected that the use of the Dresden Wavefront Analyzer in conjunction with the WaveLight Allegretto laser will be able to achieve visual acuities of 20/15 routinely, and possibly be able to achieve some acuities of 20/10, and possibly to the retinal diffraction limit of 20/6.

The WaveLight Allegretto laser is a small spot (1 mm) scanning system. It operates at 200 Hz repetition rate, and utilizes a 250 Hz active tracking system, based on an infrared camera. The tracker is pupil-based, and uses a patented illumination system to guarantee stable tracking through all stages of surgery, independent of ablation type or quality of the keratome cut. It can be selected for self-centering of the pupil center, or decentered as desired.

WaveLight is undertaking a European study of low to moderate myopia with astigmatism at 3 sites in Germany, Spain and Ireland, that will be done according to FDA protocols, for possible use in an FDA submission for U.S. marketing approval. 150 patients from -1 to -10 diopters, with 0.25 to 2 diopters of astigmatism will be included. The Dresden Wavefront Analyzer will be used on both eyes and bilateral LASIK performed, using the Chiron Hansatome, the Schwind Supratome, and the Moria CB keratome.

Schwind eye-tech-solutions

As previously noted, the Dresden Wavefront Analyzer will also be utilized with a new Schwind 6th generation scanning small spot excimer laser with active tracking. The laser will operate at 200 Hz and have a 250 Hz passive/active eye tracker, which corresponds to a reaction time of 4 ms. The local pulse repetition on a single point will be less than 35 Hz, in order to avoid local heating of the corneal tissue. It is expected that the ablation area will be quite smooth, created by a small 0.9 mm gaussian laser spot. The system will combine all standard treatments, along with customized ablations based on either topographic or aberrometric diagnostic information. According to Dr. Seiler, this new laser creates the smoothest ablations that he has seen. It is expected to be unveiled at this Spring's ASCRS meeting, at which time more details will be available.

Bausch & Lomb/Chiron/Orbtek

Not much technical information was provided about the new aberroscope being developed by B&L for use with its Chiron/Technolas excimer laser. The device demonstrated appeared to be a Hartmann-Shack type system, operating in a similar fashion as those from Autonomous, 20/10 Perfect Vision, and Dresden. Similar ablation maps were created, but no details of how this device would be linked to the Technolas laser. It is assumed that the analyzer will be combined with Orbtek's Orbscan corneal topography device, to provide total cornea and eye system aberration measurements. No information was provided about whether Bausch & Lomb intends to commercialize the aberroscope as a separate-standing diagnostic system.

Tracey Technologies

The final device shown on the AAO exhibition floor for measuring the abnormalities of the refractive system of the eye was the Tracey Ray-Tracing Refractometer. Unlike the Hartmann-Shack type devices, the Tracey ray tracing device uses the fundamental thin beam principle of optical ray tracing to measure the refractive power of the eye on a point-by-point basis. According to Tracey Technologies, its ray tracing device measures one point in the entrance pupil at a time, rather than measuring the entire entrance pupil at once, like the aberroscopes and Hartmann-Shack devices, with the possibility of data points criss-crossing with a highly aberrated eye. The ray trace device is designed to very rapidly fire a series of parallel light beams one at a time, within microseconds, into the eye, passing through the entrance pupil in an infinite selection of software selectable patterns. With this technique, the Tracey system can probe particular areas of the aperture of the eye. By design, the Tracey system can register where each "bullet" of light strikes the retina as the fovea is represented by the conjugate focal point of the system from the patient's fixation. Semiconductor photodetectors are able to detect the location of where each light ray strikes the retina and provide raw data measuring the (x,y) error distance from the ideal conjugate focus point, giving a direct measurement of refractive error for that point in the entrance pupil. Because of the high speed of the system, 64 points of light within a 6 mm pupil can be measured five times each in just over 10 ms, thus greatly increasing the accuracy and reproducibility of the system. The Tracey system can easily measure a large dynamic range of aberrations and maintain high resolution, which should provide for a significant advantage when measuring a physiological system, such as the eye, with its range of refractive errors. The Tracey system is practically a direct measure of the point-spread function of the eye, and with its retinal spot detection, can easily provide for full calculation of wavefront deformation and modulation transfer function of the eye.

Tracey Technologies expects to have its device ready for commercialization within three to six months, and for it to be priced in the range of a premium topographer.

Although all three of the techniques for measuring the aberrations of the eye -- the aberroscope, Hartmann-Shack analyzer, and the ray tracing device -- can provide a map useful for determining ablation patterns, Tracey claims that its device has a greater speed of measurement, greater reproducibility, and more flexibility through simple software selection of the desired data points of measurement. Only time will tell which type of device is preferred by the marketplace.

Techniques Under Development/in Use for Customized Ablations

Company           Wavefront   Corneal Topography Topography +
Aesculap-Meditec           X            X        Autorefractor
B&L/Technolas              X            X
LaserSight                              X
Nidek                                                   X
Schwind                    X            X
Summit/Autonomous          X
Telco                                   X
VISX                       X            X
WaveLight                  X            X 

Source: Spectrum Consulting, December 1999.